Reptin and Pontin Oligomerization and Activity Are Modulated through Histone H3 N-terminal Tail Interaction

Queval, Richard; Papin, Christophe; Dalvai, Mathieu; Bystricky, Kerstin; Humbert, Odile

doi:10.1074/jbc.m114.576785

Cited by 10 publications

(12 citation statements)

References 49 publications

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“…3.0-8.5 mol ATP min À1 mol À1 protein monomer at 40 -55 C. These rates are comparable with those published for Escherichia coli RuvB (k cat $4.8) (Marrione and Cox, 1996) and the yeast Rvb1-Rvb2 complex (k cat $2.4) (Gribun et al, 2008). However, diverse factors will play regulatory roles in vivo as, e.g., recently shown for histone H3 amino-terminal tails that modulate the activity and oligomerization of orthologs from rat or human (Queval et al, 2014). Moreover, as described for other AAA+ ATPases, most likely also ctRvb1$ctRvb2 complexes couple ATP binding and hydrolysis to interdomain conformational rearrangements and asymmetry.…”

Section: Discussionsupporting

confidence: 84%

Structural Basis for Dodecameric Assembly States and Conformational Plasticity of the Full-Length AAA+ ATPases Rvb1·Rvb2

et al. 2015

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As building blocks of diverse macromolecular complexes, the AAA+ ATPases Rvb1 and Rvb2 are crucial for many cellular activities including cancer-related processes. Their oligomeric structure and function remain unclear. We report the crystal structures of full-length heteromeric Rvb1·Rvb2 complexes in distinct nucleotide binding states. Chaetomium thermophilum Rvb1·Rvb2 assemble into hexameric rings of alternating molecules and into stable dodecamers. Intriguingly, the characteristic oligonucleotide-binding (OB) fold domains (DIIs) of Rvb1 and Rvb2 occupy unequal places relative to the compact AAA+ core ring. While Rvb1's DII forms contacts between hexamers, Rvb2's DII is rotated 100° outward, occupying lateral positions. ATP was retained bound to Rvb1 but not Rvb2 throughout purification, suggesting nonconcerted ATPase activities and nucleotide binding. Significant conformational differences between nucleotide-free and ATP-/ADP-bound states in the crystal structures and in solution suggest that the functional role of Rvb1·Rvb2 is mediated by highly interconnected structural switches. Our structures provide an atomic framework for dodecameric states and Rvb1·Rvb2's conformational plasticity.

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Section: Discussionsupporting

confidence: 84%

Structural Basis for Dodecameric Assembly States and Conformational Plasticity of the Full-Length AAA+ ATPases Rvb1·Rvb2

et al. 2015

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“…RuvBL1 and RuvBL2 proteins from mammals and yeast can co‐exist in different monomeric or oligomeric complexes comprising dimers, trimers, hexamers or double‐hexamers that can be composed as mixed multimers (Torreira et al ., ; Niewiarowski et al ., ; Queval et al ., ). Each RuvBL monomer contains three basic domains (DI, DII, DIII) (Figure a).…”

Section: Resultsmentioning

confidence: 97%

The plant Pontin and Reptin homologues, RuvBL1 and RuvBL2a, colocalize with TERT and TRB proteins in vivo, and participate in telomerase biogenesis

et al. 2019

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Summary Telomerase maturation and recruitment to telomeres is regulated by several telomerase‐ and telomere‐associated proteins. Among a number of proteins, human Pontin and Reptin play critical roles in telomerase biogenesis. Here we characterized plant orthologues of Pontin and Reptin, RuvBL1 and RuvBL2a, respectively, and show association of Arabidopsis thaliana RuvBL1 (AtRuvBL1) with the catalytic subunit of telomerase (AtTERT) in the nucleolus in vivo. In contrast to mammals, interactions between AtTERT and AtRuvBL proteins in A. thaliana are not direct and they are rather mediated by one of the Arabidopsis thaliana Telomere Repeat Binding (AtTRB) proteins. We further show that plant orthologue of dyskerin, named AtCBF5, is indirectly associated with AtTRB proteins but not with the AtRuvBL proteins in the plant nucleus/nucleolus, and interacts with the Protection of telomere 1 (AtPOT1a) in the nucleolus or cytoplasmic foci. Our genome‐wide phylogenetic analyses identify orthologues in RuvBL protein family within the plant kingdom. Dysfunction of AtRuvBL genes in heterozygous T‐DNA insertion A. thaliana mutants results in reduced telomerase activity and indicate the involvement of AtRuvBL in plant telomerase biogenesis.

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“…In particular, we were interested in exploring whether by modifying reptin's oligomeric state we would change the proteins it interacts with. 30 A number of assays could have been used to screen for novel reptin ligands, including helicase activity, ATPase activity, fragment based drug discovery, and/or high throughput competitive binding with nucleotide ligands. 31 Indeed, a recent approach has identified small molecule inhibitors of the ATPase activity of the reptin paralog, pontin.…”

Section: Discussionmentioning

confidence: 99%

Discovery of a novel ligand that modulates the protein–protein interactions of the AAA+ superfamily oncoprotein reptin

et al. 2015

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Reptin and Pontin Oligomerization and Activity Are Modulated through Histone H3 N-terminal Tail Interaction

Cited by 10 publications

References 49 publications

Structural Basis for Dodecameric Assembly States and Conformational Plasticity of the Full-Length AAA+ ATPases Rvb1·Rvb2

Structural Basis for Dodecameric Assembly States and Conformational Plasticity of the Full-Length AAA+ ATPases Rvb1·Rvb2

The plant Pontin and Reptin homologues, RuvBL1 and RuvBL2a, colocalize with TERT and TRB proteins in vivo, and participate in telomerase biogenesis

Discovery of a novel ligand that modulates the protein–protein interactions of the AAA+ superfamily oncoprotein reptin

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